Pharmacokinetics effects of chuanxiong rhizoma on warfarin in pseudo germ-free rats
In China, warfarin is usually prescribed with Chuanxiong Rhizoma for treating thromboembolism diseases. However, the reason for their combination is still being determined. The present study explored the pharmacokinetics interactions of warfarin, Chuanxiong Rhizoma, and gut microbiota in the rat mod...
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Published in | Frontiers in pharmacology Vol. 13; p. 1022567 |
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Abstract | In China, warfarin is usually prescribed with Chuanxiong Rhizoma for treating thromboembolism diseases. However, the reason for their combination is still being determined. The present study explored the pharmacokinetics interactions of warfarin, Chuanxiong Rhizoma, and gut microbiota in the rat model of middle cerebral artery occlusion (MCAO).
A total of 48 rats were randomly divided into six groups: MCAO rats orally administered warfarin (W group), pseudo germ-free MCAO rats orally administered warfarin (W-f group), MCAO rats co-administered Chuanxiong Rhizoma and warfarin (C + W group), pseudo germ-free MCAO rats co-administered Chuanxiong Rhizoma and warfarin (C + W-f group), MCAO rats co-administered warfarin and senkyunolide I (S + W group); pseudo germ-free MCAO rats co-administered warfarin and senkyunolide I (S + W-f group). After treatment, all animals' blood and stool samples were collected at different time points. The stool samples were used for 16S rRNA sequencing analysis. Ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method was established to quantify warfarin, internal standards, and the main bioactive components of Chuanxiong in blood samples. The main pharmacokinetics parameters of warfarin were calculated by DAS 2.1.1 software.
The relative abundance of
and
in the pseudo germ-free groups (W-f, C + W-f, S + W-f) was lower than that in the other three groups (W, C + W, S + W). The relative abundance of
in the W-f group was higher than that of the W group, while the relative abundance of
decreased. The relative abundance of Ruminococcaceae
and Ruminococcaceae
in the S + W-f group was lower than in the S + W group. Compared to the W group, the AUC
and C
of warfarin in the W-f group increased significantly to 51.26% and 34.58%, respectively. The AUC
and C
in the C + W group promoted 71.20% and 65.75% more than the W group. Compared to the W group, the AUC
and C
increased to 64.98% and 64.39% in the S + W group.
Chuanxiong Rhizoma and senkyunolide I (the most abundant metabolites of Chuanxiong Rhizoma aqueous extract) might affect the pharmacokinetics features of warfarin in MCAO rats through, at least partly, gut microbiota. |
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AbstractList | Aim: In China, warfarin is usually prescribed with Chuanxiong Rhizoma for treating thromboembolism diseases. However, the reason for their combination is still being determined. The present study explored the pharmacokinetics interactions of warfarin, Chuanxiong Rhizoma, and gut microbiota in the rat model of middle cerebral artery occlusion (MCAO).Methods: A total of 48 rats were randomly divided into six groups: MCAO rats orally administered warfarin (W group), pseudo germ-free MCAO rats orally administered warfarin (W-f group), MCAO rats co-administered Chuanxiong Rhizoma and warfarin (C + W group), pseudo germ-free MCAO rats co-administered Chuanxiong Rhizoma and warfarin (C + W-f group), MCAO rats co-administered warfarin and senkyunolide I (S + W group); pseudo germ-free MCAO rats co-administered warfarin and senkyunolide I (S + W-f group). After treatment, all animals’ blood and stool samples were collected at different time points. The stool samples were used for 16S rRNA sequencing analysis. Ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method was established to quantify warfarin, internal standards, and the main bioactive components of Chuanxiong in blood samples. The main pharmacokinetics parameters of warfarin were calculated by DAS 2.1.1 software.Results: The relative abundance of Allobaculum and Dubosiella in the pseudo germ-free groups (W-f, C + W-f, S + W-f) was lower than that in the other three groups (W, C + W, S + W). The relative abundance of Lactobacillus in the W-f group was higher than that of the W group, while the relative abundance of Akkermansia decreased. The relative abundance of Ruminococcaceae_UCG-014 and Ruminococcaceae_NK4A214_group in the S + W-f group was lower than in the S + W group. Compared to the W group, the AUC0-t and Cmax of warfarin in the W-f group increased significantly to 51.26% and 34.58%, respectively. The AUC0-t and Cmax in the C + W group promoted 71.20% and 65.75% more than the W group. Compared to the W group, the AUC0-t and Cmax increased to 64.98% and 64.39% in the S + W group.Conclusion: Chuanxiong Rhizoma and senkyunolide I (the most abundant metabolites of Chuanxiong Rhizoma aqueous extract) might affect the pharmacokinetics features of warfarin in MCAO rats through, at least partly, gut microbiota. Aim: In China, warfarin is usually prescribed with Chuanxiong Rhizoma for treating thromboembolism diseases. However, the reason for their combination is still being determined. The present study explored the pharmacokinetics interactions of warfarin, Chuanxiong Rhizoma, and gut microbiota in the rat model of middle cerebral artery occlusion (MCAO). Methods: A total of 48 rats were randomly divided into six groups: MCAO rats orally administered warfarin (W group), pseudo germ-free MCAO rats orally administered warfarin (W-f group), MCAO rats co-administered Chuanxiong Rhizoma and warfarin (C + W group), pseudo germ-free MCAO rats co-administered Chuanxiong Rhizoma and warfarin (C + W-f group), MCAO rats co-administered warfarin and senkyunolide I (S + W group); pseudo germ-free MCAO rats co-administered warfarin and senkyunolide I (S + W-f group). After treatment, all animals’ blood and stool samples were collected at different time points. The stool samples were used for 16S rRNA sequencing analysis. Ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method was established to quantify warfarin, internal standards, and the main bioactive components of Chuanxiong in blood samples. The main pharmacokinetics parameters of warfarin were calculated by DAS 2.1.1 software. Results: The relative abundance of Allobaculum and Dubosiella in the pseudo germ-free groups (W-f, C + W-f, S + W-f) was lower than that in the other three groups (W, C + W, S + W). The relative abundance of Lactobacillus in the W-f group was higher than that of the W group, while the relative abundance of Akkermansia decreased. The relative abundance of Ruminococcaceae _UCG-014 and Ruminococcaceae _NK4A214_group in the S + W-f group was lower than in the S + W group. Compared to the W group, the AUC 0-t and C max of warfarin in the W-f group increased significantly to 51.26% and 34.58%, respectively. The AUC 0-t and C max in the C + W group promoted 71.20% and 65.75% more than the W group. Compared to the W group, the AUC 0-t and C max increased to 64.98% and 64.39% in the S + W group. Conclusion: Chuanxiong Rhizoma and senkyunolide I (the most abundant metabolites of Chuanxiong Rhizoma aqueous extract) might affect the pharmacokinetics features of warfarin in MCAO rats through, at least partly, gut microbiota. In China, warfarin is usually prescribed with Chuanxiong Rhizoma for treating thromboembolism diseases. However, the reason for their combination is still being determined. The present study explored the pharmacokinetics interactions of warfarin, Chuanxiong Rhizoma, and gut microbiota in the rat model of middle cerebral artery occlusion (MCAO). A total of 48 rats were randomly divided into six groups: MCAO rats orally administered warfarin (W group), pseudo germ-free MCAO rats orally administered warfarin (W-f group), MCAO rats co-administered Chuanxiong Rhizoma and warfarin (C + W group), pseudo germ-free MCAO rats co-administered Chuanxiong Rhizoma and warfarin (C + W-f group), MCAO rats co-administered warfarin and senkyunolide I (S + W group); pseudo germ-free MCAO rats co-administered warfarin and senkyunolide I (S + W-f group). After treatment, all animals' blood and stool samples were collected at different time points. The stool samples were used for 16S rRNA sequencing analysis. Ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method was established to quantify warfarin, internal standards, and the main bioactive components of Chuanxiong in blood samples. The main pharmacokinetics parameters of warfarin were calculated by DAS 2.1.1 software. The relative abundance of and in the pseudo germ-free groups (W-f, C + W-f, S + W-f) was lower than that in the other three groups (W, C + W, S + W). The relative abundance of in the W-f group was higher than that of the W group, while the relative abundance of decreased. The relative abundance of Ruminococcaceae and Ruminococcaceae in the S + W-f group was lower than in the S + W group. Compared to the W group, the AUC and C of warfarin in the W-f group increased significantly to 51.26% and 34.58%, respectively. The AUC and C in the C + W group promoted 71.20% and 65.75% more than the W group. Compared to the W group, the AUC and C increased to 64.98% and 64.39% in the S + W group. Chuanxiong Rhizoma and senkyunolide I (the most abundant metabolites of Chuanxiong Rhizoma aqueous extract) might affect the pharmacokinetics features of warfarin in MCAO rats through, at least partly, gut microbiota. |
Author | Bao, Meihua Li, Zibo He, Binsheng Li, Haigang Zhou, Yi Li, Yejun Zhou, Bilan Tan, Hongyi Liao, Luanfeng |
AuthorAffiliation | 2 Department of Pharmacy , Changsha Medical University , Changsha , China 6 Department of Pharmacy , Changsha Health Vocational College , Changsha , China 4 Center of Clinical Pharmacology , The Third Xiangya Hospital , Central South University , Changsha , China 1 Hunan key laboratory of the research and development of novel pharmaceutical preparations , Changsha Medical University , Changsha , China 3 Academician Workstation , Changsha Medical University , Changsha , China 5 Department of medical laboratory , Changsha Medical University , Changsha , China |
AuthorAffiliation_xml | – name: 2 Department of Pharmacy , Changsha Medical University , Changsha , China – name: 1 Hunan key laboratory of the research and development of novel pharmaceutical preparations , Changsha Medical University , Changsha , China – name: 3 Academician Workstation , Changsha Medical University , Changsha , China – name: 6 Department of Pharmacy , Changsha Health Vocational College , Changsha , China – name: 5 Department of medical laboratory , Changsha Medical University , Changsha , China – name: 4 Center of Clinical Pharmacology , The Third Xiangya Hospital , Central South University , Changsha , China |
Author_xml | – sequence: 1 givenname: Haigang surname: Li fullname: Li, Haigang organization: Academician Workstation, Changsha Medical University, Changsha, China – sequence: 2 givenname: Yi surname: Zhou fullname: Zhou, Yi organization: Academician Workstation, Changsha Medical University, Changsha, China – sequence: 3 givenname: Luanfeng surname: Liao fullname: Liao, Luanfeng organization: Department of Pharmacy, Changsha Medical University, Changsha, China – sequence: 4 givenname: Hongyi surname: Tan fullname: Tan, Hongyi organization: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China – sequence: 5 givenname: Yejun surname: Li fullname: Li, Yejun organization: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China – sequence: 6 givenname: Zibo surname: Li fullname: Li, Zibo organization: Department of medical laboratory, Changsha Medical University, Changsha, China – sequence: 7 givenname: Bilan surname: Zhou fullname: Zhou, Bilan organization: Department of Pharmacy, Changsha Health Vocational College, Changsha, China – sequence: 8 givenname: Meihua surname: Bao fullname: Bao, Meihua organization: Academician Workstation, Changsha Medical University, Changsha, China – sequence: 9 givenname: Binsheng surname: He fullname: He, Binsheng organization: Academician Workstation, Changsha Medical University, Changsha, China |
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Keywords | pharmacokinetics chuanxiong UPLC-MS/MS gut microbiota MCAO (middle cerebral artery occlusion) warfarin |
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Snippet | In China, warfarin is usually prescribed with Chuanxiong Rhizoma for treating thromboembolism diseases. However, the reason for their combination is still... Aim: In China, warfarin is usually prescribed with Chuanxiong Rhizoma for treating thromboembolism diseases. However, the reason for their combination is still... Aim: In China, warfarin is usually prescribed with Chuanxiong Rhizoma for treating thromboembolism diseases. However, the reason for their combination is still... |
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StartPage | 1022567 |
SubjectTerms | chuanxiong gut microbiota MCAO (middle cerebral artery occlusion) pharmacokinetics Pharmacology UPLC-MS/MS warfarin |
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Title | Pharmacokinetics effects of chuanxiong rhizoma on warfarin in pseudo germ-free rats |
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